Therapy delivery devices and methods for non-damaging neural tissue conduction block

ABSTRACT

Devices and methods for blocking signal transmission through neural tissue. One step of a method includes placing a therapy delivery device into electrical communication with the neural tissue. The therapy delivery device includes an electrode contact having a high charge capacity material. A multi-phase direct current (DC) can be applied to the neural tissue without damaging the neural tissue. The multi-phase DC includes a cathodic DC phase and anodic DC phase that collectively produce a neural block and reduce the charge delivered by the therapy delivery device. The DC delivery can be combined with high frequency alternating current (HFAC) block to produce a system that provides effective, safe, long term block without inducing an onset response.

RELATED APPLICATIONS

The present application is a continuation application of U.S. patentapplication Ser. No. 15/178,633, filed on Jun. 10, 2016, which is adivisional application of U.S. patent application Ser. No. 14/408,017(now U.S. Pat. No. 9,387,322), filed on Dec. 15, 2014, which, is a U.S.National Stage application of PCT/US2013/045859, filed Jun. 14, 2013,which claims the benefit of U.S. Provisional Patent Application Ser.Nos. 61/660,383, filed Jun. 15, 2012, and 61/821,862, filed May 10,2013. The entirety of each of the aforementioned applications is herebyincorporated by reference for all purposes.

GOVERNMENT FUNDING

This work was supported, at least in part, by grant number R01-NS-074149and grant number R01-EB-002091 from the Department of Health and HumanServices, National Institutes of Health, National Institute ofNeurological Disorders and Stroke. The United States government hascertain rights in this invention.

TECHNICAL FIELD

The present invention generally relates to systems, devices and methodsfor blocking signal transmission through neural tissue, such as a nerve,and more particularly to therapy delivery systems, devices, and methodsfor using direct current to block neural signal transmission withoutdamaging the neural tissue.

BACKGROUND

Many neurological diseases are characterized by undesirable neuralactivity resulting in severe symptoms. Such diseases include spasticity,movement disorders, and chronic pain of peripheral origin. A localized,reversible, electrical nerve conduction block would be an attractive wayof addressing these conditions.

High Frequency Alternating Current (HFAC) waveforms have been shown toprovide a very localized, immediate, complete, and reversible conductionblock for motor and sensory nerve fibers in acute animal preparationswithout indications of nerve damage. However, HFAC produces a transientneural activity when turned on. This effect has been termed the “onsetresponse.” The onset response can take many seconds to diminish andcease. If an HFAC nerve block were applied to a mixed nerve, the onsetresponse could produce a painful sensation coupled with musclecontractions. The onset response has prevented the practical use of HFACblock for spasticity control and other applications. Efforts have beenmade to shorten the HFAC so that it generally lasts less than twoseconds. These methods include the use of large HFAC amplitudes, higherfrequencies (>20 kHz), and various electrode configurations. However,the initial portion of the onset response, lasting one to two seconds,is a component of HFAC block that has not been eliminated throughmodification of the waveform or electrode design alone.

A second form of electric nerve block can be achieved with directcurrents (DC). In addition to other manipulations, slowly ramping the DCamplitude over the course of a few seconds can produce a DC blockwithout evoking action potentials. This allows for DC nerve blockwithout an onset response. However, application of DC waveforms resultsin nerve damage due probably to the creation of free radicals at theelectrode-electrolyte interface after the charge injection capacity ofthe interface is exhausted and the voltage across the interface leavesthe water-window. The water-window is the specific voltage range foreach electrode-electrolyte interface that is limited by the activationenergy, or applied external voltage, necessary to produce molecularoxygen and hydrogen. An advantage of a DC block is that it can beachieved without causing an onset response by gradually ramping thecurrent amplitude. This is an effect that has not been achieved withHFAC block waveforms.

As such, a need exists for a better method of blocking neuralconduction.

SUMMARY

In general, the present invention relates to devices and methods forblocking signal transmission through a neural tissue.

In an embodiment, the present invention provides a therapy deliverydevice comprising an electrode contact comprising a high-charge capacitymaterial. The electrode contact has a geometric surface area of at leastabout 1 mm².

In another embodiment, the present invention provides a method ofblocking signal transmission through neural tissue by placing a therapydelivery device into electrical communication with the neural tissue.The therapy delivery device comprises an electrode contact comprising ahigh charge capacity material. The method further comprises applyingcurrent to the neural tissue to block signal transmission through thetissue without damaging the tissue.

In certain embodiments, a multi-phase DC current is applied to theneural tissue. Such a multi-phase DC current comprises a phase of afirst polarity configured to block signal transmission through theneural tissue and a phase of a second, opposite polarity configured toreduce the net charge transmitted by the therapy delivery device.Preferably, the subsequent current delivered has an equal and oppositecharge in opposite polarity to the first current delivered resulting ina zero net charge delivered. In certain embodiments, the multi-phase DCcurrent comprises a cathodic phase configured to block signaltransmission through the neural tissue and an anodic phase configured toreduce the net charge transmitted by the therapy delivery device. Inother embodiments, the anodic phase is configured to block signaltransmission and the cathodic phase is configured to reduce the netcharge. In certain embodiments, applying the cathodic DC phase comprisesapplying a DC having a first DC amplitude, increasing the first DCamplitude to a second DC amplitude over a first period of timeinsufficient to block neural signal transmission, maintaining the secondDC amplitude for a second period of time sufficient to block neuralsignal transmission, and decreasing the second DC amplitude to a thirdDC amplitude to reduce the net charge delivered to the neural tissue.The net charge can be reduced to substantially zero. In certainembodiments, delivering the first and second DC amplitudes over thefirst and second periods of time substantially prevents axonal firing.The duration of the recharge phase can be about equal to or greater thanthe duration of the blocking phase. In the case of a plurality ofelectrode contacts, the multi-phase DC can be continuously cycledthrough each of the electrode contacts such that a continuous block inneural signal transmission is achieved.

In other embodiments, a multi-phase DC is applied to the neural tissue,which includes a cathodic DC phase and an anodic DC phase that arecollectively configured to block neural signal transmission and reducethe charge transmitted by the therapy delivery device. The methodfurther includes applying a HFAC to the neural tissue before, during orafter application of the multi-phase DC. The HFAC has a HFAC amplitude,a HFAC frequency, and a HFAC current. The HFAC is configured to blockneural signal transmission. The combination of the multi-phase DC andthe HFAC and the order in which the multi-phase DC and the HFAC areapplied reduce an onset activity in the neural tissue associated withblocking the signal transmission through the neural tissue while alsopreventing neural damage.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of the present disclosure will becomeapparent to those of skill in the art to which the present disclosurerelates upon reading the following description with reference to theaccompanying drawings in which:

FIGS. 1A and 1B shows examples of exemplary therapy delivery devices.FIG. 1A is an exemplary therapy delivery device according to anembodiment of the present invention. FIG. 1B is another exemplarytherapy delivery device according to an embodiment of the presentinvention.

FIG. 2 is a schematic illustration depicting one example of a waveformand its application to four electrode contacts according to anembodiment of the present invention. The graph illustrates the currentdelivered by each electrode contact over time. The total time isapproximately 60 seconds. Each plateau is approximately 5 seconds inlength. The dotted lines for current indicates zero current for each theelectrode contacts. The typical current for each plateau is 1-2 mA. Thebars above the plateau indicate the period where the nerve is blocked bythe respective electrode contact. At any period of time, at least one ofthe electrode contacts is blocking the nerve and thus it is continuallyblocked. The signal from each electrode contact keeps cycling throughthe same waveform (as indicated by the dotted line for electrode contact#1).

FIGS. 3A, 3B and 3C are a schematic illustration of a DC plus HFACno-onset blocking system. FIG. 3A is a schematic illustration of anelectrode contact placed on a nerve. A gastrocnemius tendon is attachedto a force transducer to measure force. FIG. 3B is a graph depicting theno-onset block. The top trace shows tendon tension in Newtons during thetrial. The proximal stimulation (PS) trace shows when the proximalstimulation occurs (once per second). Proximal stimulation (PS) at 2Hertz (Hz) is delivered throughout the trial and the muscle twitches atthe beginning of the trial each time the PS is delivered. DC ramps down(cathodic block) and plateaus at 4.5 seconds, producing complete block.At that point, PS is still delivered, but there is no muscle force. DCblock allows HFAC to be turned on at 7.5 seconds without producing anonset response. DC is turned off and the block is maintained by theHFAC. HFAC is turned off at 17.5 second and normal conduction isrestored. FIG. 3C is a graph depicting the normal HFAC onset (when DCblock is not used).

FIGS. 4A and 4B are graphs illustrating the effect of electric nerveblock waveforms on evoked gastrocnemius muscle forces. FIG. 4A is agraph illustrating that application of HFAC alone results in a largeonset response before muscle activity is suppressed. FIG. 4B is graphillustrating that a ramped DC waveform reduces the twitches evoked by PSand minimized the onset response caused by the HFAC waveform. The barbelow the “HFAC” indicates when it is turned on. The bar under “DC”indicates when the DC is ramped from zero down to the blocking level andthen back to zero again (zero DC is not shown).

FIG. 5 is a graph illustrating the DC delivery with a pre-charge pulse,a blocking phase of opposite polarity and a final recharge phase. Thepre-charge phase lasts 2 to 26 seconds, blocking phase of oppositepolarity lasts 26-36 seconds, and a final recharge phase lasts for 36-42seconds. The top trace shows that this waveform can be accomplishedwithout producing significant unwanted activity in the nerve (nervestimulated at 1 Hz). The results are from a rat sciatic nerve. “A” inFIG. 5 is the area under the curve for the spike and the F. is the peakforce.

FIGS. 6A and 6B are graphs showing that different amplitudes of DC blockwill block different percentages of the HFAC onset response. The onsetresponse compared in FIG. 6A and FIG. 6B is the single spike that occursat about 12 seconds in FIG. 6A and at about 16 seconds in FIG. 6B.

FIGS. 7A and 7B are graphs illustrating the use of different slopes andmultiple transitions in the DC waveform to avoid activating a muscle asthe current level is varied. With steeper slopes between transitions,significant activity is induced in the nerve. This activity can bereduced or eliminated by reducing the slope of the transitions in the DCwaveform. The two lowers traces show when HFAC and DC are on. HFAC andDC are at zero when the trial starts (0 seconds).

FIG. 8 is a graph showing a DC block that is too short to block theentire HFAC onset response. The two lowers traces show when HFAC and DCare on. HFAC and DC are at zero when the trial starts (0 seconds).

FIG. 9 is a diagram depicting one example of a system for using DC toblock nerve signal transmission without damaging the nerve according toan embodiment of the present invention.

FIGS. 10A and 10B are graphs illustrating a DC block trial showing thatthe twitches elicited by proximal stimulation are blocked during theblocking phase of a trapezoidal waveform according to an embodiment ofthe present invention.

FIG. 11 is a cyclic voltammogram of several electrode contacts withdifferent Q values.

FIG. 12 is a graph depicting the viability of sciatic nerve conductionfollowing nerve block with DC (PS/DS is the muscle force ratio, which isused as an output measure to determine acute nerve damage).

FIG. 13 is a schematic illustration of potential clinical applicationsfor HFAC nerve conduction block. A block of muscle spasticity fordystonia, such as torticollis, can utilize one or more HFAC blockingelectrode contacts on the motor branches to the targeted muscles toproduce relaxation of the muscle(s). As a block for neuroma pain, theHFAC blocking electrode contact can be placed on the nerve proximal tothe neuroma. In this application, the block is delivered continuously.Motor blocks that are triggered by a recorded signal include anapplication to block intractable hiccups. The impending hiccup isrecorded as a large signal on the phrenic nerve and serves to triggerthe HFAC block of the phrenic nerve to prevent diaphragm contraction fora brief period. Control of spastic muscles in stroke, multiple sclerosisand cerebral palsy is accomplished by recording the muscle signals fromthe spastic and non-spastic muscles to determine the intended movementof the user. A partial block of the spastic muscle can be delivered toallow voluntary control.

DETAILED DESCRIPTION

In the context of the present invention, the term “patient” refers to amammal such as a human being. Also, as used herein, the term “highfrequency” with reference to alternating current (e.g. HFAC) refers tofrequencies above approximately one kiloHertz (kHz) such as, forexample, about 5 to about 50 kHz. The term “electrical communication”refers to the ability of an electric field to be transferred to, orhaving a neuromodulatory effect (e.g. blocking neural signaltransmission) within and/or one at least one neural tissue including anerve, neuron, or other type of nervous system tissue of a patient. Atherapy delivery device, described in more detail herein, can bepositioned directly on the neural tissue or near, but not in directcontact with, the neural tissue. The term “electrode contact comprisinga high charge capacity material” refers to an electrode contact thatdelivers a charge or has a “Q value” of above about 100 microcoulombs(μC) without damaging the neural tissue. As is known in the art, the Qvalue of an electrode contact is the charge capacity of the electrodecontact and is effectively the total amount of charge that can bedelivered through an electrode contact before the electrode contactstarts to transition to irreversible chemical reactions. The primaryirreversible reactions that occur are oxygen evolution or hydrogenevolution depending on the polarity of the charge being delivered. Otherirreversible reactions can occur as well such as dissolution of theelectrode material. The disclosure herein refers to the term “geometricsurface area” of an electrode contact. This refers to two-dimensionalsurface area of the electrode contact such as the smooth surface on oneside of the electrode contact as calculated by the length times thewidth of the two-dimensional outer surface of the electrode contact. The“effective or true surface area” of an electrode contact is inferredfrom the area within the curve of a cyclic voltammogram of the electrodecontact. Further, as used herein with respect to a described component,the terms “a,” “an,” and “the” include at least one or more of thedescribed component including a plurality of the described componentunless otherwise indicated. Further, the term “or” includes “and/or”unless otherwise indicated.

In general, the present invention relates to therapy delivery devicesand methods for blocking signal transmission through a neural tissue.The therapy delivery devices comprise an electrode contact comprising ahigh charge capacity material. As stated above, the electrode contacthas a Q value of above about 100 μC. In certain embodiments, theelectrode contact has a Q value of between about 1 and about 100millicoulombs (mC). In preferred embodiments, the Q value is on theorder of 10 mC. In certain embodiments, the high charge capacitymaterial has a charge injection capacity (the charge density that safelycan be delivered through the material) of about 1 to about 5 mC/cm². Incomparison, polished platinum, a non-high charge capacity material, hasa charge injection capacity of about 0.05 mC/cm². With an electrodecontact comprising a high charge capacity material, the effectivesurface area of the electrode contact is increased by several orders ofmagnitude over the geometric surface area. More charge safely can bedelivered to the neural tissue for longer periods of time compared totraditional stimulation electrodes such as those fabricated fromplatinum or stainless steel. As such, DC can be safely delivered throughmonopolar nerve cuff electrode contacts for durations as long as tenseconds without any nerve damage. Accordingly, the present inventionprovides systems, devices, and methods for providing an effective,reversible “no onset” neural block.

In particular with reference to FIGS. 1A and 1B, in an embodiment, thepresent invention provides a therapy delivery device 10 comprising anelectrode contact 12. Electrode contact 12 comprises a highcharge-capacity material. Electrode contact 12 has a geometric surfacearea of at least about 1 mm². In certain embodiments, the geometricsurface area of electrode contact 12 is between about 3 mm² to about 9mm². The electrode contact itself can be fabricated of a high chargecapacity material. Alternatively, the electrode contact can comprise abase body at least partially coated with a high charge capacity materialand preferably entirely coated with a high charge capacity material.Non-limiting examples of high charge capacity materials are platinumblack, iridium oxide, titanium nitride, tantalum,poly(ethylenedioxythiophene) and suitable combinations thereof.

As shown in FIG. 1A, therapy delivery device 10A is a spiral nerve cuffelectrode. As shown in FIG. 1B, therapy delivery device 10B is a flatinterface nerve electrode. The nerve cuff electrode can take the form ofa spiral cuff, a helical cuff, a flat interface nerve electrode, orother nerve cuff electrodes that place electrode contacts around thenerve or neural tissue. However, the therapy delivery device can haveother configurations such as a mesh, a linear rod-shaped lead,paddle-style lead, or a disc contact electrode including a multi-disccontact electrode. The therapy delivery device can also be placeddirectly into the nerve or neural tissue, such as a penetratingintraneural electrode. As shown in FIG. 1A and FIG. 1B, therapy deliverydevices 10A and 10B comprise a plurality of electrode contacts 12A and12B, respectively, however the therapy delivery device can comprise lessthan a plurality of electrode contacts. Further, the therapy deliverydevice can comprise electrode contacts that do not comprise a highcharge capacity material. The electrode contacts can either be monopolaror bipolar. In certain embodiments, the therapy delivery devicecomprises a plurality of multiple contiguous electrode contacts. In oneexample, the number of contiguous electrode contacts is four.

In general, the present invention also provides a method of blockingneural signal transmission. Such a method is distinct from activatingneural signal transmission by applying short pulses (lastingmicroseconds) to the neural tissue. A method includes placing a therapydelivery device into electrical communication with the neural tissue. Incertain embodiments, the therapy delivery device is applied directly toor in the neural tissue. In other embodiments, the therapy deliverydevice is located nearby, but not in direct contact with, the neuraltissue. The therapy delivery device has an electrode contact comprisinga high charge capacity material. The method further comprises applyingcurrent to the neural tissue to block neural signal transmission withoutdamaging the neural tissue. In certain embodiments the current is directcurrent (DC). In other embodiments, the current is DC and HFAC.Preferably, the HFAC is applied after the DC. Because a high capacitycharge material is used, the DC can be applied for longer periods oftime than previous blocking DC waveforms without damaging the neuraltissue or the electrode contact. For example, DC can be applied for atleast about ten seconds. In certain embodiments, the DC is appliedbetween about one second and about ten seconds. The DC can be appliedbetween about ten seconds and about 600 seconds.

In certain embodiments, a multi-phase DC is applied to the neural tissuewithout causing damage to the neural tissue. The multi-phase DC caninclude a cathodic DC phase and a reciprocal anodic DC phase. Thecathodic DC need not be applied first. As such, a multi-phase DC can beapplied to the neural tissue including applying an anodic DC current andthen a reciprocal cathodic DC current. One phase of the DC is configuredto produce a complete, substantially complete, or even partial nerveblock and the other phase is configured (e.g. by reversing the current)to reduce or balance a charge returned to the therapy delivery device.Exemplary multi-phase DC includes relatively slow current ramps thatfail to produce an onset response in the neural tissue. For example,with reference to FIG. 2, a slow ramp of cathodal current, followed by aplateau, followed by a slow current ramp in the anodal direction can beapplied to the neural tissue. The total net charge delivered by any ofthe electrode contacts can be equal to, or about equal to zero.Advantageously, delivery of a net zero charge is considerably safer toneural tissue. FIG. 2 illustrates waveforms having a substantiallytrapezoidal delivered by four electrode contacts (“1,” “2,” “3,” and“4”) of a therapy delivery device. Each of the cathodic and anodic DCphases begins and ends with a ramp, which prevents or substantiallyprevents any axonal firing. At the plateau of the cathodic DC phase, forexample, there is complete neural block. As discussed above, thecathodic DC phase can cause neural block and, following this phase, thecurrent is reversed (anodic DC phase) to balance the charge delivered bythe therapy delivery device. The anodic recharge time can be about equalto, or moderately longer than the cathodic block time. Moreover, thecycles of cathodic block and anodic recharge can be applied to theneural tissue sequentially for prolonged periods of time without anyneural damage. Again, the sequence of the DC phases can be reversed andthe anodic DC phase may cause the neural block and the cathodic DC phasemay balance the charge delivered by the therapy delivery device.

In some instances, the cathodic DC phase is conducted as follows. A DChaving a first DC amplitude can be applied to the neural tissue. Thefirst DC is then increased, over a first period of time, to a second DCamplitude. The DC having the first amplitude is insufficient to producea partial or complete neural block. Next, the second DC amplitude issubstantially maintained over a second period of time that is sufficientto produce a complete neural block. After the second period of time, thesecond DC amplitude is decreased to a third DC amplitude that is equalto, or about equal to, the first DC amplitude.

In an embodiment of a method, multiple contiguous electrode contacts canbe placed into electrical communication with neural tissue. Such aconfiguration may be useful where neural conduction is not entirelyblocked during the anodic or cathodic DC phase. In this case, thecathodic DC phase and the anodic DC phase can be continuously cycledamongst the electrode contacts so that there will be a continuous neuralblock without neural damage. In one example, and as shown in FIG. 2, thecathodic DC phase and the anodic DC phase can be continuously cycledamongst four contiguous monopolar electrode contacts so that there willbe a continuous neural block without neural damage.

As already noted, another aspect of the present invention can include amethod (as described above) that can be combined with HFAC delivery toreduce or eliminate an “onset response” in a subject. HFAC has beendemonstrated to provide a safe, localized, reversible, electrical neuralconduction block. HFAC, however, produces an onset response of short butintense burst of firing at the start of HFAC. Use of short durations ofDC to block the neural conduction during this HFAC onset phase caneliminate the onset problem. Though DC can produce neural block, it cancause damage to neural tissue within a short period of time.

Advantageously, the methods described above can be combined with HFAC toeliminate the onset response without neural damage. For example, amulti-phase DC can be applied to the neural tissue. As discussed above,the cathodic DC phase can be configured to produce a neural block, theanodic DC phase can be configured to balance a charge delivered by thetherapy delivery device, or vice versa. Before, during, or afterapplication of the multi-phase DC, a HFAC can be applied to the neuraltissue. The HFAC can have a HFAC amplitude, a HFAC frequency, and a HFACcurrent. The HFAC can be configured to produce a neural conduction blockin the neural tissue. The combination of the multi-phase DC and theHFAC, and the order in which the multi-phase DC and the HFAC areapplied, reduce an onset activity in the neural tissue associated withproducing the conduction neural block while also preventing neuronaldamage.

In certain embodiments, a “pre-charge” pulse is applied to the neuraltissue. In particular, a DC having a first polarity is applied to theneural tissue and then a DC having a second, opposite polarity isapplied to the neural tissue. A DC having a third polarity that is thesame as the first polarity can also be applied to the neural tissue toreduce the net charge delivered by the therapy delivery device. Thisconfiguration allows the total charge that can safely be delivered inthe second phase to be as much as twice the charge in a typical pulse.

The current in any of the above embodiments can be applied to anysuitable neural tissue in which signal transmission is desired to beblocked. For example, the neural tissue can be a component of theperipheral nervous system or the central nervous system. Regarding theperipheral nervous system, the neural tissue can be a peripheral nerveincluding cranial nerves, spinal nerves, motor efferent nerves, sensoryafferent nerves, autonomic nerves, or any suitable combination thereof.The current can also be applied to collections of neurons, such as thebrain, spinal cord or ganglia. The current can be applied to the axon,cell body or dendrites of a nerve so long as signal transmission isblocked and the neural tissue is not damaged.

The methods can be used to affect abnormal function in patients. Inparticular, methods of the present invention can be used for motor nerveblock, sensory nerve block, or autonomic block. In addition applicationsof methods of the present invention can be open loop, where control ofblock is through a switch, or closed loop, where block is controlledautomatically via one or more physiological sensors. Exemplary clinicalsystems are depicted in FIG. 13.

Motor block applications include the block of muscle spasticity instroke, cerebral palsy and multiple sclerosis. Such an application takesadvantage of the gradability and quick reversibility of HFAC block.Function can restored with a partial block of motor activity, similar tothe block produced by Botox or a phenol injection. In other cases,additional function can be provided by combining the HFAC block with anintelligent control system that varies the block based on sensedactivity. For example, overpowering flexor spasticity often preventsstroke patients from voluntarily opening their hands By monitoring themyoelectric signal of the flexor and extensor muscles, the intention ofthe patient can be identified and the finger flexors can be partiallyblocked while activating the finger extensors with electricalstimulation when hand opening is desired.

In another embodiment, methods of the present invention are used toproduce a relaxation of the urinary sphincter “on command ” An exampleof an application where this is important is in electrical stimulationsystems designed to produce bladder evacuation for individuals withspinal cord injury. In these systems, stimulation of the sacral rootsproduces bladder contraction for evacuation, but also produces unwantedsphincter contraction. The methods of the present invention can beapplied bilaterally to the pudendal nerve to prevent sphincter activityduring bladder activation. After the bladder is emptied, the block canbe turned off to restore continence. The blocking electrode contact mayalso be used as stimulation to activate a weak sphincter and improvecontinence. Nerve conduction block on the sacral sensory roots can alsobe used to prevent spontaneous bladder contraction and thus improvecontinence. Methods can also be used to control bladder-sphincterdyssynergia in spinal cord injury.

Methods of the present invention can also be used as an alternative toneurolysis procedures to relieve contractures produced by musclespasticity. For example, spastic ankle plantar flexors and hip adductorsin cerebral palsy result in a characteristic pattern of contracturesthat limit function, make hygiene difficult and can become painful.Release of gastrocnemius tightness through tendon lengthening orneurolysis is usually only performed as a last resort due to theirreversible nature of these procedures. Since the HFAC block of methodsof the present invention is reversible, it can be applied as a muchearlier method of treatment. HFAC block could be applied throughout thenight, or at specific times during the day, producing a period ofcomplete relaxation of the gastrocnemius/soleus hip adductor muscles.During ambulation the block can be turned off, allowing patients toutilize the voluntary function of these muscles for walking. Earlyintervention may prevent the development of contractures in thesemuscles, eliminating the need for irreversible procedures.

Involuntary movements and spasticity that occur in conditions such asdystonias, choreas and tics can also be modulated by HFAC nerve blockaccording to methods of the present invention. In many of theseconditions, botulinum toxin injection has become a common treatmentoption. However, the need for repeated injections every few months is asignificant disadvantage and can be quite expensive. Some cases appearto be resistant to treatment with botulinum toxin or become resistantafter repeated treatments. At present, surgical alternatives are stillutilized as a last resort in these cases. For these latter cases, HFACblock according to the present invention can provide a better treatmentmodality than irreversible surgical management and may be preferable torepeated botulinum toxin injections for some patients. An example ofthis type of application, torticollis, is shown in FIG. 13 and involvesblock of the sternocleidomastoid muscle and, in some cases, block of theposterior neck muscles.

Methods of the present invention can also be used to mitigateintractable hiccups where by blocking phrenic nerve conduction. Theimpending hiccup can be sensed through a nerve signal recording on theproximal phrenic nerve. A large volley of activity, indicating animpeding hiccup, can be used to trigger the HFAC block more distally onthe phrenic nerve. In certain embodiments, the block is only applied fora very brief period in order to block the hiccup, and thus notinterfering with normal breathing.

Regarding sensory nerve block applications, methods of the presentinvention can be used to block painful neuromas that develop followingtraumatic injury, such as limb amputation. Neuromas can be extremelypainful, and the resulting disability can be significant and difficultto treat. Since the nerve end is transected (by amputation), the nerveno longer carries useful information. Therefore, a complete block ofnerve activity is desirable.

HFAC blocks according to the present invention can be used for anypainful conduction that is presently treated with neurolysis or chemicalblocks, including cancer pain, post-herpetic neuralgia, and some casesof low back pain and headache. Some of these conditions are currentlytreated with peripheral nerve stimulation, which is not always effectiveand can produce a constant sensation due to the stimulation. With anHFAC block, a period of screening using a short acting local anestheticapplied to the nerve can be a prognosticator of HFAC success.

Regarding autonomic nerve block applications, destruction of specificcomponents of the autonomic nervous system is utilized to treat certainconditions where no good alternative treatment exists. For example,destruction of the thoracic sympathetic ganglia is used to treathyperhydrosis. Although this procedure can be successful, possibleside-effects include Homer's Syndrome. The use of HFAC nerve blockaccording to methods of the present invention at these sites allows theprocedure to be performed in a reversible manner. The side effects maybe able to be alleviated or reduced by activation of the autonomic blockonly when needed. In other embodiments, HFAC block is used for autonomicdysfunction including treatment for excessive drooling and treatment ofpancreatic cancer pain (currently treated through destruction of theceliac plexus in extreme cases).

As such, methods of the present invention can be used to reducespasticity in a patient suffering from cerebral palsy, stroke, ormultiple sclerosis, for example, by blocking signal transmission througha nerve associated with the spasticity. The methods can be used to blockmuscle spasms in spinal cord injury or post-operatively afterorthopaedic surgery to prevent involuntary contractions of the muscle.The methods can be used to block sensory signals, such as acute andchronic pain signals, in order to relieve pain. The methods can be usedto block neural pain circuits in the spinal cord or brain in order torelieve chronic pain. The methods can be used to block tremors inParkinson's Disease and related diseases by either blocking theperipheral nerves to the muscles or through block of the neural circuitsin the brain. The methods can also be used to modulate the autonomicnervous system. Other indications include improving the symptoms ofasthma in a patient suffering therefrom comprising blocking signaltransmission through nerves generating the constriction of airways inasthma.

The present invention includes data using electrode contacts fabricatedfrom high charge capacity (“Hi-Q”) materials to achieve DC nerve blockwithout damaging the nerve. In particular, in select examples,platinized Pt electrode contacts were used to achieve DC nerve blockwithout damaging the nerve even after a large number (>100) of repeatedapplications. The high charge capacity materials result in a significantincrease of the electrode contact's charge injection capacity, and arequantified in the Q value. In order to avoid nerve damage, the storedcharge was retrieved after the blocking time by inverting the currentdrive and charge-balancing the Helmholtz Double Layer (HDL).

Using a combination of Hi-Q DC electrode contacts and a HFAC electrodecontact, successful no-onset block was demonstrated, as shown in FIG. 3.In experiments with this method, more than fifty successive blocksessions without degrading nerve conduction was achieved. DC block (at2.4 mA) was repeatedly applied over the course of approximately twohours for a cumulative DC delivery of 1500 seconds with no degradationin nerve conduction. FIG. 4 shows additional data depicting successfulelimination of the onset response using the combination of HFAC and Hi-QDC nerve block.

The use of a combined HFAC and Hi-Q DC nerve block requires that the DCcan be delivered for a period of time sufficient to block the entireonset response of the HFAC. This typically lasts 1 to 10 seconds, andthus the DC should be delivered for that entire period. A method offurther extending the total plateau time over which the DC can be safelydelivered is to use a “pre-charge” pulse, as shown in FIG. 5. Thepre-charge pulse comprises delivering a DC wave of opposite polarityfrom desired block effect for a length of time up to the maximum chargecapacity of the electrode contact. The DC polarity is then reversed toproduce the block effect. However, the block can now be deliveredlonger, potentially twice as long, because the electrode contact hasbeen “pre-charged” to an opposite polarity. At the end of the prolongedblock phase, the polarity is again reversed back to the same polarity asthe pre-charge phase, and the total charge is reduced by delivery ofthis final phase. In most cases, the total net charge of this waveformwill be zero, although beneficial effects can be obtained even if thetotal net charge is not completely balanced.

Varying the level of DC can partially or fully block the onset responsefrom the HFAC, as shown in FIG. 6. This can be useful to assess thenerve health by verifying a small response even in the midst ofsignificant nerve block. The depth of the DC block can be assessedthrough this method.

Multi-Slope transitions may help avoid onset response, especially withdiscrete changes in DC-current-amplitude over time (slope) in areal-world device. This is shown in FIG. 7, which are results from arat's sciatic nerve. In these examples, the DC begins with a low slopeto prevent firing of the nerve at low amplitudes. The slope can then beincreased to reach the blocking amplitude quicker. Once DC blockamplitude has been achieved, block is maintained for the durationrequired to block the HFAC onset response. The HFAC is turned on oncethe DC has reached blocking plateau. The HFAC is turned on at theamplitude necessary to block. Once the onset response has completed, theDC is reduced, initially rapidly and then more slowly in order toprevent activation of the nerve. The DC is then slowly transitioned tothe recharge phase where the total charge injection is reduced. In thisexample, the recharge phase is at a low amplitude and lasts for over 100seconds. HFAC block can be maintained throughout this period and canthen be continued beyond the end of the DC delivery if continued nerveblock is desired. Once the total period of desired block has beencompleted (which could be many hours in some cases), the HFAC can beturned off and the nerve allowed to return to normal conductingcondition. This process can be repeated again and again as needed toproduce nerve block on command as desired to treat disease.

FIG. 8 shows that the DC is maintained throughout the period of theonset response from the HFAC in order to block the entire onsetresponse. In this example (rat sciatic nerve), the onset response lastsabout 30 seconds. The DC waveform (blue trace) initially blocks theonset response, but when the DC ramps back to zero, the onset responsebecomes apparent (at ˜50 seconds). This illustrates very long DCblocking waveforms to combine the HFAC and DC blocks to achieve ano-onset block.

According to another example, monopolar nerve cuff electrode contactswere manufactured using platinum foil. These electrode contacts werethen platinized in chloroplatinic acid solutions to create platinumblack coatings of various roughness factors from 50 to over 600. Acyclic voltammogram for each of the electrode contacts was generated todetermine the water window. The amount of charge that could be safelydelivered by these electrode contacts (the “Q value”) was estimated bycalculating the charge associated with hydrogen adsorption from −0.25Vto +0.1V vs. a standard Ag/AgCl electrode contact.

Acute experiments were performed on Sprague-Dawley rats to test theefficacy of DC nerve block with these electrode contacts. Underanaesthesia, the sciatic nerve and the gastrocnemius muscle on one sidewas dissected. Bipolar stimulating electrode contacts were placedproximally and distally on the sciatic nerve. The proximal stimulation(PS) elicited muscle twitches and allowed the quantification of motornerve block. The distal stimulation (DS) also elicited muscle twitchesand these twitches were compared with those from PS as a measure ofnerve damage under the DC electrode contact. A monopolar electrodecontact was placed between the two stimulating electrode contacts asschematically illustrated in FIG. 9. Both platinum and platinum blackelectrode contacts were tested in this location.

DC experiments were performed in rats to determine the effect of DCpulses of various current levels and durations. A current-controlledwaveform generator (Keithley Instruments, Solon, Ohio) was used tocreate the DC waveform. The waveform was a trapezoidal blocking phasefollowed by a square recharge phase as depicted in the graph of FIG.10B. The ramp up and down ensured that there was no onset firing fromthe DC. The DC parameters were chosen so that the total charge deliveredwas less than the Q value for a given electrode contact. Each cathodic(blocking) pulse was then followed by a recharge phase in which 100% ofthe charge was returned to the electrode contact by an anodic pulsemaintained at 100 μA.

The cyclic voltammogram for several of these electrode contacts in 0.1MH₂SO₄ is shown in FIG. 11. Typically Q values for these electrodecontacts ranged from 2.9 mC to 5.6 mC. In contrast, a standard Pt foilelectrode contact has a Q value of 0.035 mC.

Platinum black electrode contacts were successfully used to achieve aconduction block while maintaining the total charge below the maximum Qvalue for each electrode contact. FIGS. 10A and 10B illustrate a trialwhere complete motor nerve block was obtained using DC with a peakamplitude of 0.55 mA. The muscle twitches elicited by PS were completelyblocked during the plateau phase of the DC delivery.

FIG. 12 illustrates the effects of cumulative dosages of DC for five ofthe platinum black electrode contacts as compared to a standard platinumelectrode contact. DC was delivered as shown in FIG. 10B. Each cycle ofDC was followed by PS and DS to produce a few twitches (not shown inFIGS. 10A and 10B). The PS/DS ratio is a measure of acute nerve damage.If the nerve is conducting normally through the region under the blockelectrode contact, the ratio should be near one. The platinum electrodecontact demonstrated nerve damage in less than one minute after deliveryof less than 50 mC and the nerve did not recover in the following 30minutes. The platinum black electrode contacts do not show signs ofsignificant neural damage for the duration of each experiment, up to amaximum of 350 mC of cumulative charge delivery. Similar results wereobtained in repeated experiments using other platinum black electrodecontacts with variable Q values.

The foregoing description and examples have been set forth merely toillustrate the invention and are not intended as being limiting. Each ofthe disclosed aspects and embodiments of the present invention may beconsidered individually or in combination with other aspects,embodiments, and variations of the invention. Further, while certainfeatures of embodiments of the present invention may be shown in onlycertain figures, such features can be incorporated into otherembodiments shown in other figures while remaining within the scope ofthe present invention. In addition, unless otherwise specified, none ofthe steps of the methods of the present invention are confined to anyparticular order of performance. Modifications of the disclosedembodiments incorporating the spirit and substance of the invention mayoccur to persons skilled in the art and such modifications are withinthe scope of the present invention. Furthermore, all references citedherein are incorporated by reference in their entirety.

The invention claimed is:
 1. An electrode comprising: at least onecontact adapted to directly contact neural tissue and configured todeliver a therapy signal to the neural tissue, wherein the at least onecontact comprises a high charge capacity material that preventsformation of irreversible reaction products when the therapy signaldelivers a charge of 100 μC or more to the neural tissue.
 2. Theelectrode of claim 1, wherein the therapy signal comprises at least onedirect current (DC) with at least one polarity.
 3. The electrode ofclaim 1, wherein the therapy signal comprises a DC of a polarity and ahigh frequency alternating current (HFAC), wherein the HFAC is appliedlater in time than the DC.
 4. The electrode of claim 1, wherein the atleast one contact has a geometric surface area of at least about 1 mm².5. The electrode of claim 4, wherein the geometric surface area isbetween about 3 mm² and 9 mm².
 6. The electrode of claim 1, wherein theat least one contact is fabricated of the high charge capacity material.7. The electrode of claim 1, wherein the at least one contact comprisesa base body that at least partially is coated with the high chargecapacity material.
 8. The electrode of claim 1, wherein the high chargecapacity material is platinum black, titanium nitride, tantalum, orpoly(ethylenedioxythiophene).
 9. The electrode of claim 1, furthercomprising a nerve cuff housing the at least one contact.
 10. Theelectrode of claim 1, wherein the at least one contact is monopolar. 11.A method comprising placing at least one contact of an electrode indirect contact with neural tissue; and delivering a therapy signalthrough the at least one contact to the neural tissue; wherein the atleast one contact comprises a high charge capacity material thatprevents formation of irreversible reaction products when the therapysignal delivers a charge of 100 μC or more to the neural tissue.
 12. Themethod of claim 11, wherein the neural tissue comprises a peripheralnerve.
 13. The method of claim 11, wherein the neural tissue comprisesthe brain or spinal cord.
 14. The method of claim 11, wherein the neuraltissue comprises a motor nerve, a sensory nerve, an autonomic nerve, orany suitable combination thereof.
 15. The method of claim 11, furthercomprising blocking signal transmission through at least a portion ofthe neural tissue based on the application of the therapy signal. 16.The method of claim 11, wherein the therapy signal comprises a currentthat delivers the charge of 100 μC or more to the neural tissue.
 17. Themethod of claim 11, wherein the therapy signal is delivered for a timebetween one second and 600 seconds.
 18. The method of claim 11, whereinthe therapy signal is delivered for a time between one second and 10seconds.
 19. The method of claim 11, wherein the therapy signal isdelivered for a time of 30 seconds or more.
 20. The method of claim 11,wherein the at least one contact has a geometric surface area of atleast about 1 mm².